The issue of mast cell heterogeneity has been investigated in non-human primates by a comparative examination of lung and intestinal mast cells. These cells were obtained in parallel from the respective tissues of individual monkeys by an identical enzymatic dispersion technique. Mast cells derived from the lung differed from those derived from the intestine in that the majority of the former cell type could be stained with toluidine blue at pH 4-5, where as the intestinal mast cells in the dispersed preparations required a more acidic pH (less than 1) to display metachromasis. In addition, the lung cells exhibited an increased content of the mast cell mediator histamine. Non-human primate lung mast cells were also quantitatively more responsive to an immunologic challenge than their intestinal counterparts in that they released a higher percentage of cellular histamine and generated more leukotrient C4 on stimulation. Considerable inter-animal variation was observed between the magnitude of mediator release from both mast cell types following anaphylactic activation, but evidence for the presence in non-human primates of the phenomenon of releasability was not obtained. The responsiveness of both cell types to a range of potential non-immunologic secretagogues and anti-allergic agents, including compound 48/80, substance P, theophylline and isoprenaline, was essentially similar. We conclude that mast cell heterogeneity in higher animals may be reflected more by cytochemical rather than by functional differences between mast cell classes.